Objective With the shift toward utilization of sentinel lymph node biopsy (SLNB) in oral cavity cancer, improved techniques for intraoperative sentinel node identification are needed. This study investigates the feasibility of fluorescently labeled tilmanoscept in SLNB in an oral cancer rabbit model. Methods An animal study was designed using 21 healthy male New Zealand rabbits. Gallium‐68‐labeled tilmanocept labeled with IRDye800CW was injected submucosally into the buccal mucosa ( n = 6) or lateral tongue ( n = 7) followed by PET imaging. One hour after injection, SLNB was performed using fluorescence imaging followed by a bilateral neck dissection and sampling of non‐nodal surrounding tissue. All tissues were measured for radioactivity and fluorescence. In addition, eight rabbits were injected with delayed SLNB performed 48 h after injection. Results Buccal injections all had ipsilateral SLN drainage and tongue injections exhibited 18.2% contralateral drainage. An average of 1.9 ± 1.0 SLN (range 1–5) were identified. In addition, an average of 16.9 ± 3.3 non‐sentinel lymph nodes were removed per animal. SLNs had an average of 0.69 ± 0.60 percent‐of‐injected dose (%ID) compared with non‐sentinel nodes with 0.012 ± 0.025 %ID and surrounding tissue with 0.0067 ± 0.015 %ID. There was 98.0% agreement between sentinel lymph nodes identified using fluorescence compared to radioactivity with Cohen's kappa coefficient of 0.879. In 48‐h delayed SLNB, results were consistent with 97.8% agreement with radioactivity and Cohen's Kappa coefficient of 0.884. Fluorescence identified additional lymph nodes that were not identified by radioactivity, and with one false negative. Conclusion Fluorescent‐labeled Tc‐99 m‐tilmanocept represents a highly accurate adjunct to enhance SLNB for oral cavity cancer. Level of Evidence N/A Laryngoscope , 134:1299–1307, 2024

Introduction: Blood-brain barrier (BBB) disruption and subsequent neuro-inflammation occur following traumatic brain injury (TBI), resulting in a spectrum of human nervous system disorders. [Tc-99m]Tc-tilmanocept is a receptor-binding radiopharmaceutical FDA-approved for sentinel lymph node mapping. We hypothesize that after an intravenous (i.v.) injection, [Tc-99m]Tc-tilmanocept, will traverse a disrupted BBB and bind to CD206-bea ring microglial cells. Methods: Age-matched mice were divided into three groups: 5-days post TBI (n = 4), and 5-days post sham (n = 4), and naive controls (n = 4). IRDye800CW-labeled [Tc-99m]Tc-tilmanocept (0.15 nmol per gram body weight) and FITC-labeled bovine scrum albumin (FITC-B5A) were injected (i.v.) into each mouse. Mice were imaged with a high-resolution gamma camera for 45 min. Immediately after imaging, the brains were perfused with fixative, excised, imaged with a fluorescence scanner, assayed for radioactivity, and prepared for histology. Results: In vivo nuclear imaging, ex vivo fluorescence imaging, ex vivo gamma well counting, and histomicroscopy demonstrated enhanced tilmanocept uptake in the TBI region. The normalized [Tc-99m]Tc-tilmanocept uptake value from nuclear imaging and the maximum pixel intensity from fluorescence imaging of the TBI group ( 1.12 +/- 0.12 and 2288 +/- 278 a.u., respectively) were significantly (P < 0.04) higher than the sham group (0.64 0.28 and 1708 +/- 101 am., respectively) and the naive group (0.76 +/- 024 and 1643 +/- 391 a.u., respectively). The mean [Tc-99m]Tc-tilmanocept scaled uptake in the TBI brains (0.058 +/- 0.013%/g) was significantly (P < 0.010) higher than the scaled brain uptake of the sham group (0.031 +/- 0.011%/g) and higher (P 0.04) than the uptake of the naive group (0.020 +/- 0.002%/g). Fluorescence microscopy demonstrated increased uptake of the IRDye800CW-tilmanocept and ITTC-BSA in the TBI brain regions. Conclusion: [Tc-99m]Tc-tilmanocept traverses disrupted blood-brain barrier and localizes within the injured region. Advances in knowledge and implications for patient care: [Tc-99m]Tc-tilmanocept could serve as an imaging biomarker for TBI-associated neuroinflammation and any disease process that involves a disruption of the blood-brain barrier. (C) 2020 Elsevier Inc. All rights reserved.

Exposure to chronic hyperglycemia because of diabetes mellitus can lead to development and progression of diabetic kidney disease (DKD). We recently reported that reduced superoxide production is associated with mitochondrial dysfunction in the kidneys of mouse models of type 1 DKD. We also demonstrated that humans with DKD have significantly reduced levels of mitochondrion-derived metabolites in their urine. Here we examined renal superoxide production in a type 2 diabetes animal model, the db/db mouse, and the role of a mitochondrial protectant, MTP-131 (also called elamipretide, SS-31, or Bendavia) in restoring renal superoxide production and ameliorating DKD. We found that 18-week-old db/db mice have reduced renal and cardiac superoxide levels, as measured by dihydroethidium oxidation, and increased levels of albuminuria, mesangial matrix accumulation, and urinary H2O2. Administration of MTP-131 significantly inhibited increases in albuminuria, urinary H2O2, and mesangial matrix accumulation in db/db mice and fully preserved levels of renal superoxide production in these mice. MTP-131 also reduced total renal lysocardiolipin and major lysocardiolipin subspecies and preserved lysocardiolipin acyltransferase 1 expression in db/db mice. These results indicate that, in type 2 diabetes, DKD is associated with reduced renal and cardiac superoxide levels and that MTP-131 protects against DKD and preserves physiological superoxide levels, possibly by regulating cardiolipin remodeling.

An unmet need for the clinical management of chronic kidney disease is a predictive tool of kidney function during the first decade of the disease, when there is silent loss of glomerular function. The objective of this study was to demonstrate receptor-mediated binding of tilmanocept to CD206 within the kidney and provide evidence of kinetic sensitivity of this binding to renal function. Methods: Rats were positioned in a PET scanner with the liver and kidneys within the field of view. After an intravenous injection of Ga-68-IRDye800-tilmanocept, using 1 of 2 scaled molar doses (0.02 nmol/g, n = 5; or 0.10 nmol/g, n = 5), or coinjection (n = 3) of 68Ga-IRDye800-tilmanocept (0.10 nmol/g) and unlabeled tilmanocept (5.0 nmol/g), or a negative control, Ga-68-IRDye800-DTPA-galactosyl-dextran (0.02 nmol/g, n = 5), each animal was imaged for 20 min followed by a whole-body scan. Frozen kidney sections were stained for podocytes and CD206 using immunofluorescence. Molecular imaging of diabetic db/db mice (4.9 wk, n = 6; 7.3 wk, n = 4; 13.3 wk, n = 6) and nondiabetic db/m mice (n = 6) was performed with fluorescence-labeled Tc-99m-tilmanocept (18.5 MBq, 2.6 nmol). Thirty minutes after injection, blood, liver, kidneys, and urine were assayed for radioactivity. Renal time-activity curves were generated. Results: Rat PET whole-body images and time-activity curves of Ga-68-IRDye800-tilmanocept demonstrated receptor-mediated renal accumulation with evidence of glomerular uptake. Activity within the renal cortex persisted during the 40-min study. Histologic examination demonstrated colocalization of CD206 and IRDye800-tilmanocept within the glomerulus. The glomerular accumulation of the coinjection and the negative control studies were significantly less than the CD206-targeted agent. The db/db mice displayed a multiphasic renal time-activity curve with high urinary bladder accumulation; the nondiabetic mice exhibited renal uptake curves dominated by a single phase with low bladder accumulation. Conclusion: This study demonstrated receptor-mediated binding to the glomerular mesangial cells and kinetic sensitivity of tilmanocept to chronic renal disease. Given the role of mesangial cells during the progression of diabetic nephropathy, PET or SPECT renal imaging with radiolabeled tilmanocept may provide a noninvasive quantitative assessment of glomerular function.

Purpose The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (18F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. Patients and methods 18F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. 18F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from 18F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan–Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. Results PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan–Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with 18F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. Conclusions 18F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Molecular imaging with a fluorescent version of Tilmanocept may permit an accurate and facile detection of sentinel nodes of endometrial cancer. Tilmanocept accumulates in sentinel lymph nodes (SLN) by binding to a cell surface receptor unique to macrophages and dendritic cells. Four female Yorkshire pigs underwent cervical stromal injection of IRDye800-Tilmanocept, a molecular imaging agent tagged with near-infrared fluorescent dye and radiolabeled with gallium-68 and technetium-99m. PET/CT scans 1.5 hours post-injection provided pre-operative SLN mapping. Robotic-assisted lymphadenectomy was performed two days after injection, using the FireFly imaging system to identify nodes demonstrating fluorescent signal. After removal of fluorescent nodes, pelvic and periaortic node dissections were performed. Nodes were assayed for technetium-99m activity, and SLNs were established using the “10%-rule”, requiring that the radioactivity of additional SLNs be greater than 10% of the “hottest” SLN. Thirty-four nodal samples were assayed ex vivo for radioactivity. All the SLNs satisfying the “10%-rule” were detected using the FireFly system. Five fluorescent nodes were detected, corresponding with preoperative PET/CT scan. Three pigs had one SLN and one pig had two SLNs, with 100% concordance between fluorescence and radioactivity. Fluorescent-labeled Tilmanocept permits real-time intraoperative detection of SLNs during robotic-assisted lymphadenectomy for endometrial cancer in a porcine model. When radiolabeled with gallium-68, Tilmanocept allows for preoperative localization of SLNs using PET/CT, and shows specificity to SLNs with persistent fluorescent signal, detectable using the FireFly system, for two days post-injection. In conclusion, these findings suggest that a phase I trial in human subjects is warranted, and that a long-term goal of an intra-operative administration of non-radioactive fluorescent-labeled Tilmanocept is possible.

The primary objective was to test the ability of a laparoscopic camera system to detect the fluorescent signal emanating from sentinel lymph nodes (SLNs) approximately 2 d after injection and imaging of a positron-emitting molecular imaging agent into the submucosa of the porcine urinary bladder. Methods: Three female pigs underwent a submucosal injection of the bladder with fluorescent-tagged tilmanocept, radiolabeled with both 68Ga and 99mTc. One hour after injection, a pelvic PET/CT scan was acquired for preoperative SLN mapping. Approximately 36 h later, robotic SLN mapping was performed using a fluorescence-capable camera system. After identification of the fluorescent lymph nodes, a pelvic lymph node dissection was completed with robotic assistance. All excised nodal packets (n = 36) were assayed for 99mTc activity, which established a lymph node as an SLN. 99mTc activity was also used to calculate the amount of dye within each lymph node. Results: All of the SLNs defined by the ex vivo γ-well assay of 99mTc activity were detected by fluorescence mode imaging. The time between injection and robotic SLN mapping ranged from 32 to 38 h. A total of 5 fluorescent lymph nodes were detected; 2 pigs had 2 fluorescent lymph nodes and 1 pig exhibited a single lymph node. Four of the 5 SLNs exhibited increased SUVs of 12.4–139.0 obtained from PET/CT. The dye content of the injection sites ranged from 371 to 1,441 pmol, which represented 16.5%–64.1% of the injected dose; the amount of dye within the SLNs ranged from 8.5 to 88 pmol, which was equivalent to 0.38%–3.91% of the administered dose. Conclusion: Fluorescent-labeled 68Ga-tilmanocept allows for PET imaging and real-time intraoperative detection of SLNs during robotic surgery.

Aim A national audit of quantitative thyroid uptake imaging was conducted by the Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine in 2014/2015. The aims of the audit were to measure and assess the variability in thyroid uptake results across the UK and to compare local protocols with British Nuclear Medicine Society (BNMS) guidelines.Participants and methods Participants were invited through a combination of emails on a public mailbase and targeted invitations from regional co-ordinators. All participants were given a set of images from which to calculate quantitative measures and a spreadsheet for capturing results. The image data consisted of two sets of 10 anterior thyroid images, half of which were acquired after administration of Tc-99m-pertechnetate and the other half after administration of I-123-iodide. Images of the administration syringes or thyroid phantoms were also included.Results In total, 54 participants responded to the audit. The median number of scans conducted per year was 50. A majority of centres had at least one noncompliance in comparison with BNMS guidelines. Of most concern was the widespread lack of injection-site imaging. Quantitative results showed that both intersite and intrasite variability were low for the Tc-99m dataset. The coefficient of quartile deviation was between 0.03 and 0.13 for measurements of overall percentage uptake. Although the number of returns for the I-123 dataset was smaller, the level of variability between participants was greater (the coefficient of quartile deviation was between 0.17 and 0.25).Conclusion A UK-wide audit showed that thyroid uptake imaging is still a common test in the UK. It was found that most centres do not adhere to all aspects of the BNMS practice guidelines but that quantitative results are reasonably consistent for Tc-99m-based scans. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

Fluorescence imaging is one of the most versatile and widely used visualization methods in biomedical research. However, tissue autofluorescence is a major obstacle confounding interpretation of in vivo fluorescence images. The unusually long emission lifetime (5-13 μs) of photoluminescent porous silicon nanoparticles can allow the time-gated imaging of tissues in vivo , completely eliminating shorter-lived (< 10 ns) emission signals from organic chromophores or tissue autofluorescence.Here, using a conventional animal imaging system not optimized for such long-lived excited states, we demonstrate improvement of signal to background contrast ratio by > 50-fold in vitro and by > 20-fold in vivo when imaging porous silicon nanoparticles. Time-gated imaging of porous silicon nanoparticles accumulated in a human ovarian cancer xenograft following intravenous injection is demonstrated in a live mouse. The potential for multiplexing of images in the time domain by using separate porous silicon nanoparticles engineered with different excited state lifetimes is discussed. probes that target diseased tissues has also shown promising results in clinical settings, such as the early detection of breast cancer,

Purpose To determine patient, vendor, and institutional factors that influence computed tomography (CT) radiation dose. Materials and Methods The relevant institutional review boards approved this HIPAA-compliant study, with waiver of informed consent. Volume CT dose index (CTDIvol) and effective dose in 274 124 head, chest, and abdominal CT examinations performed in adult patients at 12 facilities in 2013 were collected prospectively. Patient, vendor, and institutional characteristics that could be used to predict (a) median dose by using linear regression after log transformation of doses and (b) high-dose examinations (top 25% of dose within anatomic strata) by using modified Poisson regression were assessed. Results There was wide variation in dose within and across medical centers. For chest CTDIvol, overall median dose across all institutions was 11 mGy, and institutional median dose was 7-16 mGy. Models including patient, vendor, and institutional factors were good for prediction of median doses (R2 = 0.31-0.61). The specific institution where the examination was performed (reflecting the specific protocols used) accounted for a moderate to large proportion of dose variation. For chest CTDIvol, unadjusted median CTDIvol was 16.5 mGy at one institution and 6.7 mGy at another (adjusted relative median dose, 2.6 mGy [95% confidence interval: 2.5, 2.7]). Several variables were important predictors that a patient would undergo high-dose CT. These included patient size, the specific institution where CT was performed, and the use of multiphase scanning. For example, while 49% of patients (21 411 of 43 696) who underwent multiphase abdominal CT had a high-dose examination, 8% of patients (4977 of 62 212) who underwent single-phase CT had a high-dose examination (adjusted relative risk, 6.20 [95% CI: 6.17, 6.23]). If all patients had been examined with single-phase CT, 69% (18 208 of 26 388) of high-dose examinations would have been eliminated. Patient size, institutional-specific protocols, and multiphase scanning were the most important predictors of dose (change in R2 = 8%-32%), followed by manufacturer and iterative reconstruction (change in R2, 0.2%-15.0%). Conclusion CT doses vary considerably within and across facilities. The primary factors that influenced dose variation were multiphase scanning and institutional protocol choices. It is unknown if the variation in these factors influenced diagnostic accuracy. © RSNA, 2016.

PURPOSE:To summarize data on computed tomographic (CT) radiation doses collected from consecutive CT examinations performed at 12 facilities that can contribute to the creation of reference levels.MATERIALS AND METHODS:The study was approved by the institutional review boards of the collaborating institutions and was compliant with HIPAA. Radiation dose metrics were prospectively and electronically collected from 199 656 consecutive CT examinations in 83 181 adults and 3871 consecutive CT examinations in 2609 children at the five University of California medical centers during 2013. The median volume CT dose index (CTDIvol), dose-length product (DLP), and effective dose, along with the interquartile range (IQR), were calculated separately for adults and children and stratified according to anatomic region. Distributions for DLP and effective dose are reported for single-phase examinations, multiphase examinations, and all examinations.RESULTS:For adults, the median CTDIvol was 50 mGy (IQR, 37-62 mGy) for the head, 12 mGy (IQR, 7-17 mGy) for the chest, and 12 mGy (IQR, 8-17 mGy) for the abdomen. The median DLPs for single-phase, multiphase, and all examinations, respectively, were as follows: head, 880 mGy · cm (IQR, 640-1120 mGy · cm), 1550 mGy · cm (IQR, 1150-2130 mGy · cm), and 960 mGy · cm (IQR, 690-1300 mGy · cm); chest, 420 mGy · cm (IQR, 260-610 mGy · cm), 880 mGy · cm (IQR, 570-1430 mGy · cm), and 550 mGy · cm (IQR 320-830 mGy · cm); and abdomen, 580 mGy · cm (IQR, 360-860 mGy · cm), 1220 mGy · cm (IQR, 850-1790 mGy · cm), and 960 mGy · cm (IQR, 600-1460 mGy · cm). Median effective doses for single-phase, multiphase, and all examinations, respectively, were as follows: head, 2 mSv (IQR, 1-3 mSv), 4 mSv (IQR, 3-8 mSv), and 2 mSv (IQR, 2-3 mSv); chest, 9 mSv (IQR, 5-13 mSv), 18 mSv (IQR, 12-29 mSv), and 11 mSv (IQR, 6-18 mSv); and abdomen, 10 mSv (IQR, 6-16 mSv), 22 mSv (IQR, 15-32 mSv), and 17 mSv (IQR, 11-26 mSv). In general, values for children were approximately 50% those for adults in the head and 25% those for adults in the chest and abdomen.CONCLUSION:These summary dose data provide a starting point for institutional evaluation of CT radiation doses.

The rapid development of fluorescence imaging technologies requires concurrent improvements in the performance of fluorescent probes. Quantum dots have been extensively used as an imaging probe in various research areas because of their inherent advantages based on unique optical and electronic properties. However, their clinical translation has been limited by the potential toxicity especially from cadmium. Here, a versatile bioimaging probe is developed by using highly luminescent cadmium‐free CuInSe2/ZnS core/shell quantum dots conjugated with CGKRK (Cys–Gly–Lys–Arg–Lys) tumor‐targeting peptides. This probe exhibits excellent photostability, reasonably long circulation time, minimal toxicity, and strong tumor‐specific homing property. The most important feature of this probe is that it shows distinctive versatility in tumor‐targeted multimodal imaging including near‐infrared, time‐gated, and two‐photon imaging in different tumor models. In a glioblastoma mouse model, the targeted probe clearly denotes tumor boundaries and positively labels a population of diffusely infiltrating tumor cells, suggesting its utility in precise tumor detection during surgery. This work lays a foundation for potential clinical translation of the probe.

OBJECTIVE To investigate positron emission tomography/computed tomography (PET/CT) preoperative imaging and intraoperative detection of a fluorescent-labeled receptor-targeted radiopharmaceutical in a prostate cancer animal model.MATERIALS AND METHODS Three male beagle dogs underwent an intraprostatic injection of fluorescent-tagged tilmanocept, radiolabeled with both gallium Ga-68 and technetium Tc-99m. One hour after injection, a pelvic PET/CT scan was performed for preoperative sentinel lymph node (SLN) mapping. The definition of SLN was a standardized uptake value that exceeded 5% of the lymph node with the highest standardized uptake value. Thirty-six hours later, we performed robotic-assisted SLN dissection using a fluorescence-capable camera system. Fluorescent lymph nodes were clipped, the abdomen was opened, and the pelvic and retroperitoneal nodes were excised. All excised nodal packets were assayed by in vitro nuclear counting and reported as the percentage of injected dose.RESULTS Preoperative PET/CT imaging identified a median of 3 SLNs per animal. All SLNs (100%) identified by the PET/CT were fluorescent during robotic-assisted lymph node dissection. Of all fluorescent nodes visualized by the camera system, 9 of 12 nodes (75%) satisfied the 5% rule defined by the PET/CT scan. The 2 lymph nodes that did not qualify accumulated < 0.002% of the injected dose.CONCLUSION Fluorescent-labeled tilmanocept has optimal logistic properties to obtain preoperative PET/CT and subsequent real-time intraoperative confirmation during robotic-assisted SLN dissection. UROLOGY 84: 982.e9-e982.e14, 2014. (C) 2014 Elsevier Inc.

An ideal substance to provide convenient and accurate targeting for sentinel lymph node (SLN) mapping during robotic-assisted surgery has yet to be found. We used an animal model to determine the ability of the FireFly camera system to detect fluorescent SLNs after administration of a dual-labeled molecular imaging agent. Methods: We injected the footpads of New Zealand White rabbits with 1.7 or 8.4 nmol of tilmanocept labeled with Tc-99m and a near-infrared fluorophore, IRDye800CW. One and 36 h after injection, popliteal lymph nodes, representing the SLNs, were dissected with the assistance of the FireFly camera system, a fluorescence-capable endoscopic imaging system. After excision of the paraaortic lymph nodes, which represented non-SLNs, we assayed all lymph nodes for radioactivity and fluorescence intensity. Results: Fluorescence within all popliteal lymph nodes was easily detected by the FireFly camera system. Fluorescence within the lymph channel could be imaged during the 1-h studies. When compared with the paraaortic lymph nodes, the popliteal lymph nodes retain greater than 95% of the radioactivity at both 1 and 36 h after injection. At both doses (1.7 and 8.4 nmol), the popliteal nodes had higher (P < 0.050) optical fluorescence intensity than the paraaortic nodes at the 1- and 36-h time points. Conclusion:The FireFly camera system can easily detect tilmanocept labeled with a near-infrared fluorophore at least 36 h after administration. This ability will permit image acquisition and subsequent verification of fluorescence-labeled SLNs during robotic-assisted surgery.

INTRODUCTION:The Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine has conducted a multicentre, multivendor audit to evaluate the use of resolution recovery software from several manufacturers when applied to myocardial perfusion data with half the normal counts acquired under a variety of clinical protocols in a range of departments. The objective was to determine whether centres could obtain clinical results with half-count data processed with resolution recovery software that were equivalent to those obtained using their normal protocols.MATERIALS AND METHODS:Sixteen centres selected 50 routine myocardial perfusion studies each, from which the Nuclear Medicine Software Quality Group generated simulated half-count studies using Poisson resampling. These half-count studies were reconstructed using resolution recovery and the clinical reports compared with the original reports from the full-count data. A total of 769 patient studies were processed and compared.RESULTS:Eight centres found only a small number of clinically relevant discrepancies between the two reports, whereas eight had an unacceptably high number of discrepancies. There were no significant differences in acquisition parameters between the two groups, although centres finding a high number of discrepancies were more likely to perform both rest and stress scans on normal studies.CONCLUSION:Half of the participating centres could potentially make use of resolution recovery to reduce the administered activity for myocardial perfusion scans without changing their routine acquisition protocols. The other half could consider adjusting the reconstruction parameters used with their resolution recovery software if they wish to use reduced activity successfully.

384 Objectives There is an unmet need for imaging specific sites of inflammation and fibrosis in the kidney. Glomerular mesangial cells reside behind a fenestrated endothelial barrier and form the central stalk of the glomerulus. They regulate glomerular blood flow, as well as provide structural support and immune surveillance of invading pathogens. This latter function is consistent with the role of CD206, the receptor for [99mTc]tilmanocept (FDA approval 2013). The objective of this study is to determine if glomerular mesangial cells are the site of renal accumulation of tilmanocept. Methods Three rats were injected (iv) with IRDye800-labeled [68Ga]tilmanocept (0.10 nmol/g, 0.1 - 0.3 mCi). After 20 mins of PET imaging (Vista DR) over the kidneys and a 5-min static image over the bladder, each rat was euthanized and frozen sections of both kidneys were immunofluorescently stained for podocytes (Alexa-488), and CD206 (Alexa-647). Renal time-SUV curves were generated and the time to reach 90 percent of the peak value (T90) was calculated. Results Time-SUV curves demonstrated accumulation within the renal cortex with plateau SUVs ranging from 11 to 19 (median = 13.7). The T90 values ranged from 3.2 to 7.9 min (median = 4.25 min). The cortical activity was retained for 25 mins with no evidence of filtration; absent renal pelvis or urinary bladder activity. Histologic examination demonstrated co-localization of CD206 and fluorescent-labeled tilmanocept within glomerular compartments in a mesangial-type distribution. Conclusions This study demonstrated mesangial cell accumulation of tilmanocept. Given the significant role of mesangial cells during the development of fibrotic, inflammatory, and diabetic nephropathies, SPECT or PET renal imaging with radiolabeled tilmanocept may offer a novel receptor-based imaging biomarker to monitor the progression of glomerular disease. Research Support P50 CA114745